News|Articles|September 24, 2026 (Updated: September 24, 2026)

Remigromig noninferior to ranibizumab in phase 2b/3 BRUNELLO DME trial

Key Takeaways

Both remigromig doses were noninferior to 0.5-mg ranibizumab on mean BCVA change from baseline at week 52 in BRUNELLO.
Rates of PDR, vitreous hemorrhage, and discontinuations due to adverse events were higher with remigromig than ranibizumab.
Merck did not release letter gains, between-group differences, or P values; full results are slated for AAO 2026.
Remigromig is an investigational tri-specific antibody designed to activate the Wnt pathway, a novel mechanism in DME.

Remigromig met its BRUNELLO primary end point in DME, with higher PDR and vitreous hemorrhage rates than ranibizumab.

What did the BRUNELLO trial show for remigromig in diabetic macular edema?

Both doses of remigromig (MK-3000, formerly EYE103; Merck) met the primary end point of the pivotal phase 2b/3 BRUNELLO trial in adults with diabetic macular edema (DME), Merck announced September 24, 2026.¹ At week 52, the 0.5-mg and 0.8-mg doses each independently demonstrated noninferiority to 0.5-mg ranibizumab for mean change from baseline in best-corrected visual acuity (BCVA).¹

Remigromig is an investigational tetravalent, tri-specific antibody designed to activate the Wingless-related integration site (Wnt) pathway, which is involved in repair and maintenance of the blood-retinal barrier. BRUNELLO is the first of two phase 2b/3 trials of the agent in DME.¹ Merck and EyeBio, now a wholly owned Merck subsidiary, announced the trial's initiation in 2024 on the basis of results from the open-label phase 1/2 AMARONE study, when the agent was referred to as Restoret.²

BRUNELLO (NCT06571045) is a randomized, double-masked, multicenter trial comparing two dose levels of intravitreal remigromig with active control ranibizumab (Lucentis) in adults with DME.^1,3 The trial enrolled 984 participants, who were randomized 1:1:1 to 0.5 mg remigromig, 0.8 mg remigromig, or 0.5 mg ranibizumab every four weeks for the first year. In year 2, treatment frequency will shift according to a personalized treatment interval algorithm.¹

Eligible participants were adults 18 years or older with type 1 or type 2 diabetes, a hemoglobin A1c of 12% or less, and a decrease in vision in the study eye attributed primarily to DME.³ The primary end point is mean change in BCVA from baseline to week 52 in the study eye, measured with standardized Early Treatment Diabetic Retinopathy Study (ETDRS) testing.¹

Merck did not report mean letter gains, between-group differences, the noninferiority margin, or P values in the topline announcement.¹ Donald J. D'Amico, MD, chair of ophthalmology at Weill Cornell Medicine, will present the year 1 results at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting in New Orleans on October 10.^1,4Merck also plans to discuss the findings with regulatory authorities.¹

Remigromig safety profile and adverse events in BRUNELLO

According to Merck, both remigromig doses were generally well tolerated. However, higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig arms compared with ranibizumab. The company stated further analyses to characterize these findings are underway.¹

Addressing the higher rates of PDR and vitreous hemorrhage, Margaret Chang, MD, a retina specialist and clinical trial investigator at Retinal Consultants Medical Group, Sacramento, CA, told Modern Retina, "This is not unexpected given that the anti-VEGF pathway is not targeted by remigromig." While full results are still to come at AAO, she said the findings are likely a manifestation of the natural progression of diabetic retinopathy over time rather than an effect of the drug itself. She added she does not think retina specialists would expect remigromig to supplant anti-VEGF therapy and panretinal photocoagulation in patients who progress to PDR.

Safety is always an important consideration before adopting any new therapy, according to Chang. In her view, even a more efficacious therapy "would need to be as safe as our current anti-VEGF therapies for there to be widespread adoption."

The topline announcement did not include event counts or percentages by treatment arm. It also did not report rates of intraocular inflammation, endophthalmitis, retinal detachment, or intraocular pressure elevation. Secondary end point data, including anatomic outcomes, were likewise not disclosed.¹

"Despite available therapies, up to 40% of patients with diabetic macular edema do not fully respond and remain at risk of continued vision loss," said David Guyer, MD, founder, chief executive officer, and president of EyeBio, in the announcement.^1,2

In clinical practice, many of these patients cycle through several different anti-VEGF agents and intravitreal steroid therapies without complete resolution, which can frustrate both patients and physicians, Chang said. Adjunctive therapies such as focal laser or surgical intervention are sometimes used depending on the morphology of the edema, but in some difficult cases the edema remains chronic even with consistent treatment. A drug targeting another mechanism of action could help patients with persistent edema despite anti-VEGF therapy, she said, and could potentially provide an additive benefit even for patients who respond to anti-VEGF agents.

Dean Y. Li, president of Merck Research Laboratories, described remigromig as a potential first novel mechanism of action for retinal vascular diseases in more than two decades.¹ A second pivotal phase 2b/3 trial, BAROLO (NCT06957080), is ongoing in patients with DME.¹ Remigromig is also under evaluation in the phase 2 SUPER TUSCAN proof-of-concept study (NCT07205887) in patients with neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion.¹

Merck is separately developing MK-8748 (Tiespectus; EYE201), a bispecific antibody designed to activate the Tie2 pathway and inhibit VEGF.¹ The agent is in two pivotal phase 2b/3 trials for neovascular age-related macular degeneration, TORRONTES (NCT07496567) and MALBEC (NCT07440225), and two pivotal phase 3 trials for DME, SANGIOVESE (NCT07705555) and SYRAH (NCT07705607).¹